tbuckley/cabot-search huggingface dataset:
Canonical Wnt signaling promotes HSC glycolysis and liver fibrosis through an LDH-A/HIF-1α transcriptional complex
Authors: Feixia Wang, Li Chen, Desong Kong, Xiaojin Zhang, Siwei Xia, Baoyu Liang, Yang Li, Ya Zhou, Zili Zhang, Jiangjuan Shao, Shizhong Zheng, Feng Zhang
Journal: Hepatology (2023)

Background and Aims: Aerobic glycolysis reprogramming occurs during HSC activation, but how it is initiated and sustained remains unknown. We investigated the mechanisms by which canonical Wnt signaling regulated HSC glycolysis and the therapeutic implication for liver fibrosis. Approach and Results: Glycolysis was examined in HSC-LX2 cells upon manipulation of Wnt/β-catenin signaling. Nuclear translocation of lactate dehydrogenase A (LDH-A) and its interaction with hypoxia-inducible factor-1α (HIF-1α) were investigated using molecular simulation and site-directed mutation assays. The pharmacological relevance of molecular discoveries was intensified in primary cultures, rodent models, and human samples. HSC glycolysis was enhanced by Wnt3a but reduced by β-catenin inhibitor or small interfering RNA (siRNA). Wnt3a-induced rapid transactivation and high expression of LDH-A dependent on TCF4. Wnt/β-catenin signaling also stimulated LDH-A nuclear translocation through importin β2 interplay with a noncanonical nuclear location signal of LDH-A. Mechanically, LDH-A bound to HIF-1α and enhanced its stability by obstructing hydroxylation-mediated proteasome degradation, leading to increased transactivation of glycolytic genes. The Gly28 residue of LDH-A was identified to be responsible for the formation of the LDH-A/HIF-1α transcription complex and stabilization of HIF-1α. Furthermore, LDH-A-mediated glycolysis was required for HSC activation in the presence of Wnt3a. Results in vivo showed that HSC activation and liver fibrosis were alleviated by HSC-specific knockdown of LDH-A in mice. β-catenin inhibitor XAV-939 mitigated HSC activation and liver fibrosis, which were abrogated by HSC-specific LDH-A overexpression in mice with fibrosis. Conclusions: Inhibition of HSC glycolysis by targeting Wnt/β-catenin signaling and LDH-A had therapeutic promise for liver fibrosis.
Intersectional Disparities in Emergency Medicine Residents’ Performance Assessments by Race, Ethnicity, and Sex
Authors: Elle Lett, Nguyen Khai Tran, Nkemjika Nweke, Mytien Nguyen, Jung G. Kim, Eric Holmboe, William McDade, Dowin Boatright
Journal: JAMA Network Open (2023)

Previous studies have demonstrated sex-specific disparities in performance assessments among emergency medicine (EM) residents. However, less work has focused on intersectional disparities by ethnoracial identity and sex in resident performance assessments.To estimate intersectional sex-specific ethnoracial disparities in standardized EM resident assessments.This retrospective cohort study used data from the Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education Milestones (Milestones) assessments to evaluate ratings for EM residents at 128 EM training programs in the US. Statistical analyses were conducted in June 2020 to January 2023.Training and assessment environments in EM residency programs across comparison groups defined by ethnoracial identity (Asian, White, or groups underrepresented in medicine [URM], ie, African American/Black, American Indian/Alaska Native, Hispanic/Latine, and Native Hawaiian/Other Pacific Islander) and sex (female/male).Mean Milestone scores (scale, 0-9) across 6 core competency domains: interpersonal and communications skills, medical knowledge, patient care, practice-based learning and improvement, professionalism, and system-based practice. Overall assessment scores were calculated as the mean of the 6 competency scores.The study sample comprised 128 ACGME-accredited programs and 16 634 assessments for 2708 EM residents of which 1913 (70.6%) were in 3-year and 795 (29.4%) in 4-year programs. Most of the residents were White (n = 2012; 74.3%), followed by Asian (n = 477; 17.6%), Hispanic or Latine (n = 213; 7.9%), African American or Black (n = 160; 5.9%), American Indian or Alaska Native (n = 24; 0.9%), and Native Hawaiian or Other Pacific Islander (n = 4; 0.1%). Approximately 14.3% (n = 386) and 34.6% (n = 936) were of URM groups and female, respectively. Compared with White male residents, URM female residents in 3-year programs were rated increasingly lower in the medical knowledge (URM female score, -0.47; 95% CI, -0.77 to -0.17), patient care (-0.18; 95% CI, -0.35 to -0.01), and practice-based learning and improvement (-0.37; 95% CI, -0.65 to -0.09) domains by postgraduate year 3 year-end assessment; URM female residents in 4-year programs were also rated lower in all 6 competencies over the assessment period.This retrospective cohort study found that URM female residents were consistently rated lower than White male residents on Milestone assessments, findings that may reflect intersectional discrimination in physician competency evaluation. Eliminating sex-specific ethnoracial disparities in resident assessments may contribute to equitable health care by removing barriers to retention and promotion of underrepresented and minoritized trainees and facilitating diversity and representation among the emergency physician workforce.
Sentinel Node Biopsy for Early Breast Cancer—A SOUND for De-escalation
Authors: Seema A. Khan
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Physiologic changes in the hepatopulmonary syndrome before and after liver transplant: A longitudinal and predictor analysis
Authors: Xun Zhao, Sreelakshmi Kotha, Dhruv Nayyar, Xiayi Ma, Leslie Lilly, Hélène Castel, Samir Gupta
Journal: Hepatology (2023)

Background and Aims: Hepatopulmonary syndrome (HPS) is a common complication of liver disease defined by abnormal oxygenation and intrapulmonary vascular dilatation, treated with liver transplantation. Little is known about changes in HPS physiological parameters over time. We sought to describe baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological parameters before and after transplant, and predictors of changes in oxygenation. Approach and Results: This was a retrospective cohort study in the Canadian HPS Program (n = 132). Rates of change after diagnosis were: −3.7 (−6.4, −0.96) mm Hg/year for partial pressure of arterial oxygen (PaO 2 ); −26 (−96, 44) m/year for 6-minute walk distance, and 3.3% (−6.6, −0.011) predicted/year for diffusion capacity. Noninvasive shunt of ≥ 20% predicted a slower PaO 2 decline by 0.88 (0.36, 1.4) mm Hg/month. We identified 2 PaO 2 deterioration classes—“very severe disease, slow decliners” (PaO 2 45.0 mm Hg; −1.0 mm Hg/year); and “moderate disease, steady decliners” (PaO 2 65.5 mm Hg; −2.5 mm Hg/year). PaO 2 increased by 6.5 (5.3, 7.7) mm Hg/month in the first year after transplant. The median time to normalization was 149 (116, 184) days. Posttransplant improvement in PaO 2 was 2.5 (0.1, 4.9) mm Hg/month faster for every 10 mm Hg greater pretransplant orthodeoxia. Conclusions: We present a large and long longitudinal data analysis in HPS. In addition to rates of physiological decline and improvement before and after liver transplantation, we present novel predictors of PaO 2 decline and improvement rates. Our findings enhance our understanding of the natural history of HPS and provide pathophysiologic clues. Importantly, they may assist providers in prognostication and prioritization before and after transplant.
Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers
Authors: Marliese Alexander, Sam Harris, Craig Underhill, Javier Torres, Sharad Sharma, Nora Lee, HuiLi Wong, Richard Eek, Michael Michael, Jeanne Tie, Jennifer Rogers, Alexander G. Heriot, David Ball, Michael MacManus, Rory Wolfe, Benjamin J. Solomon, Kate Burbury
Journal: JAMA Oncology (2023)

Thromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers.
Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength
Authors: Hirofumi Asano, Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Ryota Iwasaki, Yoshifumi Noda, Hiroki Kato, Koki Ichihashi, Hiroyuki Tomita, Masaharu Murata, Takashi Mori, Masayuki Matsuo
Journal: Clinical Cancer Research (2023)

Abstract Purpose: An accurate and noninvasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice. Experimental Design: MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2–bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS, and histopathology were performed. Results: The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI, and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments. Conclusions: Deuterium MRI at 1.5T proved feasible to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.
Primary Thromboprophylaxis in People With Cancer—Where Next?
Authors: Alok A. Khorana
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Can variants, reinfection, symptoms and test types affect COVID-19 diagnostic performance? A large-scale retrospective study of AG-RDTs during circulation of Delta and Omicron variants, Czechia, December 2021 to February 2022
Authors: Tomáš Kliegr, Jiří Jarkovský, Helena Jiřincová, Jaroslav Kuchař, Tomáš Karel, David Chudán, Stanislav Vojíř, Michal Zavřel, Ondřej Šanca, Ruth Tachezy
Journal: Eurosurveillance (2023)

BackgroundThe sensitivity and specificity of selected antigen detection rapid diagnostic tests (AG-RDTs) for SARS-CoV-2 were determined in the unvaccinated population when the Delta variant was circulating. Viral loads, dynamics, symptoms and tissue tropism differ between Omicron and Delta.AimWe aimed to compare AG-RDT sensitivity and specificity in selected subgroups during Omicron vs Delta circulation.MethodsWe retrospectively paired AG-RDT results with PCRs registered in Czechia's Information System for Infectious Diseases from 1 to 25 December 2021 (Delta, n = 20,121) and 20 January to 24 February 2022 (Omicron, n = 47,104).ResultsWhen confirmatory PCR was conducted on the same day as AG-RDT as a proxy for antigen testing close to peak viral load, the average sensitivity for Delta was 80.4% and for Omicron 81.4% (p < 0.05). Sensitivity in vaccinated individuals was lower for Omicron (OR = 0.94; 95% confidence interval (CI): 0.87-1.03), particularly in reinfections (OR = 0.83; 95% CI: 0.75-0.92). Saliva AG-RDT sensitivity was below average for both Delta (74.4%) and Omicron (78.4%). Tests on the European Union Category A list had higher sensitivity than tests in Category B. The highest sensitivity for Omicron (88.5%) was recorded for patients with loss of smell or taste, however, these symptoms were almost 10-fold less common than for Delta. The sensitivity of AG-RDTs performed on initially asymptomatic individuals done 1, 2 or 3 days before a positive PCR test was consistently lower for Omicron compared with Delta.ConclusionSensitivity for Omicron was lower in subgroups that may become more common if SARS-CoV-2 becomes an endemic virus.
Cardiovascular Imaging in Contemporary Cardio-Oncology: A Scientific Statement From the American Heart Association
Authors: Daniel Addison, Tomas G. Neilan, Ana Barac, Marielle Scherrer-Crosbie, Tochi M. Okwuosa, Juan C. Plana, Kerryn W. Reding, Viviany R. Taqueti, Eric H. Yang, Vlad G. Zaha
Journal: Circulation (2023)

Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.
Nirmatrelvir or Molnupiravir Use and Severe Outcomes From Omicron Infections
Authors: Dan-Yu Lin, Francois Abi Fadel, Shuaiqi Huang, Alex T. Milinovich, Gretchen L. Sacha, Patricia Bartley, Abhijit Duggal, Xiaofeng Wang
Journal: JAMA Network Open (2023)

Ritonavir-boosted nirmatrelvir and molnupiravir are currently used in the US and in other countries to treat nonhospitalized patients who have mild-to-moderate COVID-19 and who are at high risk for progression to severe disease. The associations of these 2 oral antiviral drugs with hospitalization and death resulting from infection with new SARS-CoV-2 Omicron subvariants, particularly BQ.1.1 and XBB.1.5, are unknown.To assess the association of nirmatrelvir or molnupiravir use with the risks of hospitalization and death among patients infected with new Omicron subvariants.This was a cohort study of patients who received a diagnosis of COVID-19 at Cleveland Clinic from April 1, 2022, to February 20, 2023 (during which the Omicron variant evolved from BA.2 to BA.4/BA.5, then to BQ.1/BQ.1.1, and finally to XBB/XBB.1.5) and who were at high risk of progressing to severe disease, with follow-up through 90 days after diagnosis. The final date for follow-up data collection was February 27, 2023.Treatment with ritonavir-boosted nirmatrelvir or molnupiravir.The primary outcome was time to death. The secondary outcome was time to either hospitalization or death. The association of either nirmatrelvir or molnupiravir use with each outcome was measured by the hazard ratio (HR) adjusted for demographic factors, socioeconomic status, date of COVID-19 diagnosis, coexisting medical conditions, COVID-19 vaccination status, and previous SARS-CoV-2 infection.There were 68 867 patients (29 386 [42.7%] aged ≥65 years; 26 755 [38.9%] male patients; 51 452 [74.7%] non-Hispanic White patients). Thirty of 22 594 patients treated with nirmatrelvir, 27 of 5311 patients treated with molnupiravir, and 588 of 40 962 patients who received no treatment died within 90 days of Omicron infection. The adjusted HRs of death were 0.16 (95% CI, 0.11-0.23) for nirmatrelvir and 0.23 (95% CI, 0.16-0.34) for molnupiravir. The adjusted HRs of hospitalization or death were 0.63 (95% CI, 0.59-0.68) for nirmatrelvir and 0.59 (95% CI, 0.53-0.66) for molnupiravir. The associations of both drugs with both outcomes were observed across subgroups defined by age, race and ethnicity, date of COVID-19 diagnosis, vaccination status, previous infection status, and coexisting conditions.These findings suggest that the use of either nirmatrelvir or molnupiravir is associated with reductions in mortality and hospitalization in patients infected with Omicron, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions. Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.
Thermal/ultrasound-triggered release of liposomes loaded with Ganoderma applanatum polysaccharide from microbubbles for enhanced tumour ablation
Authors: Jiani Yuan, Lei Ding, Lu Han, Lina Pang, Peidi Zhang, Xiao Yang, Haijing Liu, Minjuan Zheng, Yunfei Zhang, Wen Luo
Journal: Journal of Controlled Release (2023)
Bioactive signalling lipids as drivers of chronic liver diseases
Authors: Eleanna Kaffe, Annamaria Tisi, Christiana Magkrioti, Vassilis Aidinis, Wajahat Z. Mehal, Richard A. Flavell, Mauro Maccarrone
Journal: Journal of Hepatology (2023)

Lipids are important in multiple cellular functions, with most having structural or energy storage roles. However, a small fraction of lipids exert bioactive roles through binding to G protein-coupled receptors and induce a plethora of processes including cell proliferation, differentiation, growth, migration, apoptosis, senescence and survival. Bioactive signalling lipids are potent modulators of metabolism and energy homeostasis, inflammation, tissue repair and malignant transformation. All these events are involved in the initiation and progression of chronic liver diseases. In this review, we focus specifically on the roles of bioactive lipids derived from phospholipids (lyso-phospholipids) and poly-unsaturated fatty acids (eicosanoids, pro-resolving lipid mediators and endocannabinoids) in prevalent chronic liver diseases (alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis and hepatocellular carcinoma). We discuss the balance between pathogenic and beneficial bioactive lipids as well as potential therapeutic targets related to the agonism or antagonism of their receptors.
Fungal allergen sensitization: Prevalence, risk factors, and geographic variation in the United States
Authors: Kenny Kwong, Matthew Robinson, Adam Sullivan, Stanley Letovsky, Andrew H. Liu, Andre Valcour
Journal: Journal of Allergy and Clinical Immunology (2023)

Many fungal species are associated with the pathogenesis of allergic disease, yet most epidemiologic studies on IgE-mediated fungal sensitization have only included a few species.
Federated electronic health records for the European Health Data Space
Authors: René Raab, Arne Küderle, Anastasiya Zakreuskaya, Ariel D Stern, Jochen Klucken, Georgios Kaissis, Daniel Rueckert, Susanne Boll, Roland Eils, Harald Wagener, Bjoern M Eskofier
Journal: The Lancet Digital Health (2023)

The European Commission's draft for the European Health Data Space (EHDS) aims to empower citizens to access their personal health data and share it with physicians and other health-care providers. It further defines procedures for the secondary use of electronic health data for research and development. Although this planned legislation is undoubtedly a step in the right direction, implementation approaches could potentially result in centralised data silos that pose data privacy and security risks for individuals. To address this concern, we propose federated personal health data spaces, a novel architecture for storing, managing, and sharing personal electronic health records that puts citizens at the centre-both conceptually and technologically. The proposed architecture puts citizens in control by storing personal health data on a combination of personal devices rather than in centralised data silos. We describe how this federated architecture fits within the EHDS and can enable the same features as centralised systems while protecting the privacy of citizens. We further argue that increased privacy and control do not contradict the use of electronic health data for research and development. Instead, data sovereignty and transparency encourage active participation in studies and data sharing. This combination of privacy-by-design and transparent, privacy-preserving data sharing can enable health-care leaders to break the privacy-exploitation barrier, which currently limits the secondary use of health data in many cases.